EP0424159A2 - Aseptic processing of allograft bone and tissue - Google Patents

Aseptic processing of allograft bone and tissue Download PDF

Info

Publication number
EP0424159A2
EP0424159A2 EP90311464A EP90311464A EP0424159A2 EP 0424159 A2 EP0424159 A2 EP 0424159A2 EP 90311464 A EP90311464 A EP 90311464A EP 90311464 A EP90311464 A EP 90311464A EP 0424159 A2 EP0424159 A2 EP 0424159A2
Authority
EP
European Patent Office
Prior art keywords
tissue
bone
sterilization
allograft bone
allograft
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Ceased
Application number
EP90311464A
Other languages
German (de)
French (fr)
Other versions
EP0424159A3 (en
Inventor
John P. Callen
Robert K. O'leary
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Osteotech Inc
Original Assignee
Osteotech Inc
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Osteotech Inc filed Critical Osteotech Inc
Publication of EP0424159A2 publication Critical patent/EP0424159A2/en
Publication of EP0424159A3 publication Critical patent/EP0424159A3/en
Ceased legal-status Critical Current

Links

Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L2/00—Methods or apparatus for disinfecting or sterilising materials or objects other than foodstuffs or contact lenses; Accessories therefor
    • A61L2/0005—Methods or apparatus for disinfecting or sterilising materials or objects other than foodstuffs or contact lenses; Accessories therefor for pharmaceuticals, biologicals or living parts
    • A61L2/0011—Methods or apparatus for disinfecting or sterilising materials or objects other than foodstuffs or contact lenses; Accessories therefor for pharmaceuticals, biologicals or living parts using physical methods
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L2/00—Methods or apparatus for disinfecting or sterilising materials or objects other than foodstuffs or contact lenses; Accessories therefor
    • A61L2/0005—Methods or apparatus for disinfecting or sterilising materials or objects other than foodstuffs or contact lenses; Accessories therefor for pharmaceuticals, biologicals or living parts
    • A61L2/0011—Methods or apparatus for disinfecting or sterilising materials or objects other than foodstuffs or contact lenses; Accessories therefor for pharmaceuticals, biologicals or living parts using physical methods
    • A61L2/0029—Radiation
    • A61L2/0035—Gamma radiation
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L2/00—Methods or apparatus for disinfecting or sterilising materials or objects other than foodstuffs or contact lenses; Accessories therefor
    • A61L2/0005—Methods or apparatus for disinfecting or sterilising materials or objects other than foodstuffs or contact lenses; Accessories therefor for pharmaceuticals, biologicals or living parts
    • A61L2/0082—Methods or apparatus for disinfecting or sterilising materials or objects other than foodstuffs or contact lenses; Accessories therefor for pharmaceuticals, biologicals or living parts using chemical substances
    • A61L2/0094—Gaseous substances
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L2/00—Methods or apparatus for disinfecting or sterilising materials or objects other than foodstuffs or contact lenses; Accessories therefor
    • A61L2/02—Methods or apparatus for disinfecting or sterilising materials or objects other than foodstuffs or contact lenses; Accessories therefor using physical phenomena
    • A61L2/04—Heat
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L2/00—Methods or apparatus for disinfecting or sterilising materials or objects other than foodstuffs or contact lenses; Accessories therefor
    • A61L2/02—Methods or apparatus for disinfecting or sterilising materials or objects other than foodstuffs or contact lenses; Accessories therefor using physical phenomena
    • A61L2/08—Radiation
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L2/00—Methods or apparatus for disinfecting or sterilising materials or objects other than foodstuffs or contact lenses; Accessories therefor
    • A61L2/16—Methods or apparatus for disinfecting or sterilising materials or objects other than foodstuffs or contact lenses; Accessories therefor using chemical substances
    • A61L2/20—Gaseous substances, e.g. vapours
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
    • A61L27/36—Materials for grafts or prostheses or for coating grafts or prostheses containing ingredients of undetermined constitution or reaction products thereof, e.g. transplant tissue, natural bone, extracellular matrix

Definitions

  • This invention relates to allograft bone and tissue and more particularly to the aseptic processing of allograft bone and musculoskeletal tissue prior to the implantation.
  • allograft bone and tissue have become a relatively widely utilized medical procedure.
  • Bone and tissue allografts are used to repair or replace defective or damaged bones, tendons, ligaments and the like.
  • the range of allograft transplants includes entire joints, sections of long bone, bone chips for surgical procedures such as spinal fusion and craniotomies, bone dust used in dental repair and/or reconstruction and musculoskeletal soft tissue such as ligaments and tendons.
  • Bone or tissue may be recovered using sterile technique in a sterile environment or a nonsterile area requiring secondary (final) sterilization of tissue prior to transplantation.
  • the major advantages of sterile recovery include (1) the bone or tissue retains its natural sterility and (2) there is no need for secondary final product sterilization that may alter biological or biomechanical properties or leave undesirable residues.
  • High-dose irradiation and high dose ethylene oxide i.e. high dose toxic sterilization techniques, however, can infringe upon the bone or tissues' biologic properties and also can disrupt collagen cross-linkage that is important to mechanical strength.
  • Another object of this invention is to provide a novel method for processing allograft bone or tissue which avoids the detrimental effects of high dose toxic sterilization techniques and which provides sterile products having maximum structural integrity, biomechanical properties and bioactivity.
  • an aseptic method for processing allograft bone or tissue comprising the steps of:
  • Bone and musculoskeletal tissue to be processed in accordance with the present invention are procured, typically by trained personnel, under surgically sterile conditions, from donor cadavers. Once procured, the bone and tissue is ready to be processed in accordance with the aseptic process of the present invention.
  • the allograft bone or tissue is subjected to a sterilization procedure prior to further aseptic processing of the same.
  • Sterilization procedures contemplated by the present invention include any such procedure which is capable of killing microorganisms, but which does not substantially interfere with the physical, chemical and biological properties, such as the osteogenic properties, of the bony tissue.
  • Included within the definition of microorganisms intended to be killed by the sterilization step of the present process are all vegetative and spore forming microorganisms including viruses.
  • Typical sterilization procedures encompassed by the present invention include irradiation, such as gamma radiation, electron beam radiation, ultraviolet radiation and the like, chemical sterilization such as ethylene oxide, formaldehyde, vapor phase hydrogen peroxide, chlorine dioxide, ethanol, ozone, treatment with surface active agents, such as quaternary agents, phenolic agents, glutaraldehyde and the like and thermal procedures such as ultrapasteurization.
  • irradiation such as gamma radiation, electron beam radiation, ultraviolet radiation and the like
  • chemical sterilization such as ethylene oxide, formaldehyde, vapor phase hydrogen peroxide, chlorine dioxide, ethanol, ozone
  • treatment with surface active agents such as quaternary agents, phenolic agents, glutaraldehyde and the like
  • thermal procedures such as ultrapasteurization.
  • treatment of the allograft bone or tissue comprises exposure of the allograft material to gamma radiation, such as from a cobalt-60 source or a cesium-137 source, at a dosage level sufficient to kill microorganisms but insufficient to cause substantial deterioration of the bone.
  • gamma radiation such as from a cobalt-60 source or a cesium-137 source
  • dose levels are generally within the range of from about 0.1 to about 2 megarads and, preferably about 1.0 to about 1.6 megarads.
  • the accepted standard of sterility is defined in terms of probability of survival wherein the probability relates to the probable number of test units containing one viable organism.
  • the usually accepted definition of secondary or terminal sterility is one viable microorganism per million test units.
  • the effective amount of gamma radiation for allograft bone can range, for example from about 0.1 megarads to a maximum dose below that level which would cause substantial chemical, physical or biological deterioration to the allograft bone, i.e. about 2 megarads.
  • the amount of gamma radiation necessary to achieve the one per thousand survival is about 1.0 megarads
  • the amount of gamma radiation necessary to achieve the one per million survival rate is about 1.6 megarads.
  • E-beam electron beam
  • Such a procedure would involve, for example, exposing the bone or tissue to the E-beam (typically a 5 MeV electron accelerator). * 90°F - 135°F
  • Chemical sterilization procedures are also within the scope of the process of the present invention. More specifically in the case of ethylene oxide, the bone or tissue is, for example, placed under vacuum while 650 mg./liter of ethylene oxide is introduced into the chamber for about 1 to 2 hours at a temperature of e.g.32°C - 57°C* after which the gas is removed by vacuum. Similarly, formaldehyde, chlorine dioxide or ozone could be employed as the sterilization gas in place of the ethylene oxide. Vapor phase hydrogen peroxide may also be employed as the sterilant herein.
  • the bone or tissue is placed in a vacuum chamber and, for example, a 30% H2O2 liquid solution is vaporized to gas as it enters the chamber at 32°C - 57°C* whereby the gas decomposes and the vacuum dissipates.
  • a 30% H2O2 liquid solution is vaporized to gas as it enters the chamber at 32°C - 57°C* whereby the gas decomposes and the vacuum dissipates.
  • Another chemical sterilization technique within the scope of the present invention includes soaking the bone or tissue in ethanol e.g. 70% ethanol, while the bone or tissue is maintained at a low temperature.
  • Other sterilization treatments include soaking in aqueous solutions of quaternary agents, phenolic agents, glutaraldehyde and the like.
  • the bone or tissue is maintained at a temperature which is low enough to prevent denaturization. Typically these temperatures are below 40 o C and are preferably 0 o C or below. Most preferably, irradiation sterilization in accordance with the present invention is carried out on bone or tissue which is maintained in a frozen state, e.g. packed in dry-ice during the sterilization process.
  • aseptic cleansing subsequent to sterilization of the bone or tissue is defined as including processing such as rinsing the sterilized bone and tissue with water, preferably sterile water for injection, debridement to remove soft tissue and attachments and further processing such as shaping.
  • the debrided bone or tissue may be defatted and/or demineralized and/or milled or ground into chips or bone powder.
  • Defatting is commonly carried out by contacting (e.g. soaking) the bone or tissue with a defatting solution.
  • Conventional defatting solutions include lipid solvents such as alcohols.
  • the bone may be demineralized, if desired. Demineralization is commonly carried out by soaking in acid solution in which the necessary hydrogen ion concentration is maintained while agitating the acid.
  • all allograft bone and tissue is measured or weighed, final sterility tested and packaged.
  • Processed allograft bone and tissue is typically preserved by freezing or by freeze drying.
  • allograft bone and musculoskeletal tissue can be processed in accordance with the present invention including cortical and/or cancellous bone tissue, bone and tendon, ribs, tibia, femur, humerus, fascia lata and the like. *65°F
  • the aseptic cleansing step of the present method is carried out in cleanrooms.
  • a cleanroom is an enclosure specially designed to maintain an aseptic environment.
  • the aseptic allograft processing for purposes of the present invention is preferably carried out in a class 10 cleanroom.
  • the class number indicate the number of airborne particulates in a size range of 0.3 microns or larger that are allowed per cubic foot.
  • a Class 10 cleanroom allows no more than 10 particles per cubic foot of air.
  • the air is of such high quality that no viable microorganisms are allowed.
  • the cleanroom temperature is preferably maintained at about 18°C*and the humidity is preferably maintained at about 40%. Sterilization in accordance with the present invention need not be carried out in a cleanroom, as defined above, although may be if desired.

Abstract

The present invention comprises a method for processing allograft bone or tissue, said method comprising the steps of:
  • (i) subjecting allograft bone or tissue to sterilization, said sterilization sufficient to kill microorganisms but insufficient to cause substantial physical, chemical or biological deterioration of the allograft bone or tissue; and
  • (ii) aseptically processing the sterilized allograft bone or tissue resulting from step (i).

Description

  • This invention relates to allograft bone and tissue and more particularly to the aseptic processing of allograft bone and musculoskeletal tissue prior to the implantation.
  • Recently, the transplantation of allograft bone and tissue has become a relatively widely utilized medical procedure. Bone and tissue allografts are used to repair or replace defective or damaged bones, tendons, ligaments and the like. Thus, the range of allograft transplants includes entire joints, sections of long bone, bone chips for surgical procedures such as spinal fusion and craniotomies, bone dust used in dental repair and/or reconstruction and musculoskeletal soft tissue such as ligaments and tendons.
  • The biological and biomechanical quality of allograft tissue depends largely on the retrieval, preservation and storage methods employed. Bone or tissue may be recovered using sterile technique in a sterile environment or a nonsterile area requiring secondary (final) sterilization of tissue prior to transplantation. The major advantages of sterile recovery include (1) the bone or tissue retains its natural sterility and (2) there is no need for secondary final product sterilization that may alter biological or biomechanical properties or leave undesirable residues.
  • The most frequently used methods of secondary final product sterilization include exposure to high-dose irradiation or high dose (high concentration) ethylene oxide. High-dose irradiation and high dose ethylene oxide, i.e. high dose toxic sterilization techniques, however, can infringe upon the bone or tissues' biologic properties and also can disrupt collagen cross-linkage that is important to mechanical strength.
  • Accordingly, methods for processing allograft bone and tissue which provide surgically sterile products and which do not interfere with the natural integrity or bioactivity, i.e. do not interfere with the osteogenic properties, of the allograft bone or tissue are highly desired.
  • Therefore, it is one object of the present invention to provide a novel method for processing allograft bone or musculoskeletal tissue.
  • Another object of this invention is to provide a novel method for processing allograft bone or tissue which avoids the detrimental effects of high dose toxic sterilization techniques and which provides sterile products having maximum structural integrity, biomechanical properties and bioactivity.
  • These and other objects are achieved herein by an aseptic method for processing allograft bone or tissue comprising the steps of:
    • (i) subjecting allograft bone or tissue to sterilization, said sterilization being sufficient to kill microorganisms, but insufficient to cause substantial physical chemical or biological deterioration of the allograft bone or tissue followed by:
    • (ii) aseptic cleansing of the allograft bone or tissue resulting from step (i).
  • Bone and musculoskeletal tissue to be processed in accordance with the present invention are procured, typically by trained personnel, under surgically sterile conditions, from donor cadavers. Once procured, the bone and tissue is ready to be processed in accordance with the aseptic process of the present invention.
  • Thus, in accordance with the present invention, the allograft bone or tissue is subjected to a sterilization procedure prior to further aseptic processing of the same. Sterilization procedures contemplated by the present invention include any such procedure which is capable of killing microorganisms, but which does not substantially interfere with the physical, chemical and biological properties, such as the osteogenic properties, of the bony tissue. Included within the definition of microorganisms intended to be killed by the sterilization step of the present process are all vegetative and spore forming microorganisms including viruses. Typical sterilization procedures encompassed by the present invention include irradiation, such as gamma radiation, electron beam radiation, ultraviolet radiation and the like, chemical sterilization such as ethylene oxide, formaldehyde, vapor phase hydrogen peroxide, chlorine dioxide, ethanol, ozone, treatment with surface active agents, such as quaternary agents, phenolic agents, glutaraldehyde and the like and thermal procedures such as ultrapasteurization.
  • The preferred sterilization procedure for the purposes of the present invention is low dose irradiation and particularly low doses of gamma radiation. Thus, in accordance with the preferred method of the present invention, treatment of the allograft bone or tissue comprises exposure of the allograft material to gamma radiation, such as from a cobalt-60 source or a cesium-137 source, at a dosage level sufficient to kill microorganisms but insufficient to cause substantial deterioration of the bone. For the purposes of the present invention such dose levels are generally within the range of from about 0.1 to about 2 megarads and, preferably about 1.0 to about 1.6 megarads.
  • Since absolute sterilization is impossible to attain, the accepted standard of sterility is defined in terms of probability of survival wherein the probability relates to the probable number of test units containing one viable organism. The usually accepted definition of secondary or terminal sterility is one viable microorganism per million test units. However, with the aseptic process of the present invention one microorganism per thousand test units is acceptable. Therefore, the effective amount of gamma radiation for allograft bone can range, for example from about 0.1 megarads to a maximum dose below that level which would cause substantial chemical, physical or biological deterioration to the allograft bone, i.e. about 2 megarads. Thus, in accordance with the present process, for example, with a bioburden of 100 microorganisms per test unit, the amount of gamma radiation necessary to achieve the one per thousand survival is about 1.0 megarads, and the amount of gamma radiation necessary to achieve the one per million survival rate is about 1.6 megarads.
  • As stated above, other irradiation sterilization procedures contemplated within the scope of the present invention include electron beam (E-beam) irradiation. Such a procedure would involve, for example, exposing the bone or tissue to the E-beam (typically a 5 MeV electron accelerator).
    * 90°F - 135°F
  • Chemical sterilization procedures are also within the scope of the process of the present invention. More specifically in the case of ethylene oxide, the bone or tissue is, for example, placed under vacuum while 650 mg./liter of ethylene oxide is introduced into the chamber for about 1 to 2 hours at a temperature of e.g.32°C - 57°C* after which the gas is removed by vacuum. Similarly, formaldehyde, chlorine dioxide or ozone could be employed as the sterilization gas in place of the ethylene oxide. Vapor phase hydrogen peroxide may also be employed as the sterilant herein. In this case, the bone or tissue is placed in a vacuum chamber and, for example, a 30% H₂O₂ liquid solution is vaporized to gas as it enters the chamber at 32°C - 57°C* whereby the gas decomposes and the vacuum dissipates. Another chemical sterilization technique within the scope of the present invention includes soaking the bone or tissue in ethanol e.g. 70% ethanol, while the bone or tissue is maintained at a low temperature. Other sterilization treatments include soaking in aqueous solutions of quaternary agents, phenolic agents, glutaraldehyde and the like.
  • In the embodiment of the present invention wherein irradiation is utilized as the sterilization means, it is preferred that the bone or tissue is maintained at a temperature which is low enough to prevent denaturization. Typically these temperatures are below 40oC and are preferably 0oC or below. Most preferably, irradiation sterilization in accordance with the present invention is carried out on bone or tissue which is maintained in a frozen state, e.g. packed in dry-ice during the sterilization process.
  • Subsequent to sterilization as described hereinbefore, the resultant sterilized bone or tissue is now aseptically cleansed whereby the bone or tissue is processed, inter alia, to substantially free the bone or tissue of dead bacteria and other microorganisms, as well as pyrogens. It is to be understood herein that for the purposes of the present invention and in accordance with the present invention, aseptic cleansing subsequent to sterilization of the bone or tissue, is defined as including processing such as rinsing the sterilized bone and tissue with water, preferably sterile water for injection, debridement to remove soft tissue and attachments and further processing such as shaping. Optionally, if desired, the debrided bone or tissue may be defatted and/or demineralized and/or milled or ground into chips or bone powder. Defatting is commonly carried out by contacting (e.g. soaking) the bone or tissue with a defatting solution. Conventional defatting solutions include lipid solvents such as alcohols. Following defatting, the bone may be demineralized, if desired. Demineralization is commonly carried out by soaking in acid solution in which the necessary hydrogen ion concentration is maintained while agitating the acid.
  • Subsequently, all allograft bone and tissue is measured or weighed, final sterility tested and packaged. Processed allograft bone and tissue is typically preserved by freezing or by freeze drying.
  • Various types of allograft bone and musculoskeletal tissue can be processed in accordance with the present invention including cortical and/or cancellous bone tissue, bone and tendon, ribs, tibia, femur, humerus, fascia lata and the like.
    *65°F
  • Preferably, the aseptic cleansing step of the present method is carried out in cleanrooms. A cleanroom is an enclosure specially designed to maintain an aseptic environment. More particularly, the aseptic allograft processing for purposes of the present invention is preferably carried out in a class 10 cleanroom. The class number indicate the number of airborne particulates in a size range of 0.3 microns or larger that are allowed per cubic foot. Thus a Class 10 cleanroom allows no more than 10 particles per cubic foot of air. The air is of such high quality that no viable microorganisms are allowed. The cleanroom temperature is preferably maintained at about 18°C*and the humidity is preferably maintained at about 40%. Sterilization in accordance with the present invention need not be carried out in a cleanroom, as defined above, although may be if desired.

Claims (7)

1. A method for processing allograft bone or musculoskeletal tissue, said method comprising the steps of:
(i) subjecting allograft bone or musculoskeletal tissue to sterilization, said sterilization being sufficient to kill microorganisms but insufficient to cause substantial physical, chemical or biological deterioration of the allograft bone or musculoskeletal tissue; and
(ii) aseptically cleansing the sterilized allograft bone or musculoskeletal tissue resulting from step (i).
2. A method according to claim 1 wherein said sterilization is carried out chemically, thermally or by irradiation.
3. A method according to claim 2 wherein said sterilization is carried out by gamma radiation.
4. A method according to claim 3 wherein said gamma radiation is derived from cobalt-60 gamma ray source.
5. A method according to any one of the preceding claims wherein said aseptic cleansing step (ii) includes rinsing the sterilized allograft bone or musculoskeletal tissue with sterile water.
6. A method according to any one of the preceding claims wherein said aseptic cleansing of step (ii) includes debridement and defatting of the sterilized bone or musculoskeletal tissue.
7. A method according to any one of the preceding claims wherein said aseptic cleansing of step (ii) includes demineralization.
EP19900311464 1989-10-19 1990-10-18 Aseptic processing of allograft bone and tissue Ceased EP0424159A3 (en)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
US42433989A 1989-10-19 1989-10-19
US424339 1989-10-19

Publications (2)

Publication Number Publication Date
EP0424159A2 true EP0424159A2 (en) 1991-04-24
EP0424159A3 EP0424159A3 (en) 1991-11-06

Family

ID=23682271

Family Applications (1)

Application Number Title Priority Date Filing Date
EP19900311464 Ceased EP0424159A3 (en) 1989-10-19 1990-10-18 Aseptic processing of allograft bone and tissue

Country Status (2)

Country Link
EP (1) EP0424159A3 (en)
JP (1) JPH03170156A (en)

Cited By (16)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0544926A1 (en) * 1990-06-20 1993-06-09 Chiron Adatomed Pharmazeutische und Medizintechnische Gesellschaft mbH Process and device for sterilizing implants
WO1997027882A1 (en) * 1996-01-31 1997-08-07 Steris Corporation Method of sterilization of bone tissue
FR2752382A1 (en) * 1996-08-16 1998-02-20 Assist Publ Hopitaux De Paris PROCESS FOR PROCESSING PRODUCTS OF HUMAN OR ANIMAL ORIGIN FOR THERAPEUTIC USE
US5741782A (en) * 1996-03-29 1998-04-21 Cryolife, Inc. Antibiotic cocktail and method of use
WO2001091819A1 (en) * 2000-05-29 2001-12-06 Augustinus Bader Method for producing a recipient-specific tissue transplant
KR20020011164A (en) * 2000-08-01 2002-02-08 이건일 Method for Manufacturing bone graft
WO2002070024A1 (en) * 2001-01-04 2002-09-12 Osteotech, Inc. Method for sterilizing bioactive materials
US6482584B1 (en) 1998-11-13 2002-11-19 Regeneration Technologies, Inc. Cyclic implant perfusion cleaning and passivation process
US6613278B1 (en) 1998-11-13 2003-09-02 Regeneration Technologies, Inc. Tissue pooling process
US6652818B1 (en) 1998-11-13 2003-11-25 Regeneration Technologies, Inc. Implant sterilization apparatus
WO2008008436A1 (en) * 2006-07-13 2008-01-17 Abbott Cardiovascular Systems Inc. Reduced temperature sterilization of stents
US7648676B2 (en) 2004-04-20 2010-01-19 Rti Biologics, Inc. Process and apparatus for treating implants comprising soft tissue
BE1024277B1 (en) * 2016-12-26 2018-01-11 Theracell Consulting Sprl Automated method for producing human or animal tissue for grafts.
CN109191409A (en) * 2018-07-25 2019-01-11 北京市商汤科技开发有限公司 Image procossing, network training method, device, electronic equipment and storage medium
US10420652B2 (en) 2014-10-09 2019-09-24 Dr. Panagiotis Pedoulias Bone scaffold improvements
RU2785112C2 (en) * 2016-12-26 2022-12-02 Тераселл Консалтинг Спрл Automated method for obtaining human or animal tissues for transplantations

Families Citing this family (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
AU2001259031B2 (en) * 2000-03-23 2006-04-13 Clearant, Inc. Methods for sterilizing biological materials

Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0012959A1 (en) * 1978-12-16 1980-07-09 Intermedicat GmbH Method of preparation of collagen-based bone substitute material with improved biological stability and bone substitute material obtained by this method
DE3014123A1 (en) * 1980-04-12 1981-10-29 B. Braun Melsungen Ag, 3508 Melsungen Scleroprotein e.g. collagen, keratin or elastin transplants prodn. - involving treatment with glycerol or polyethylene glycol to improve biological stability
US4456589A (en) * 1982-07-08 1984-06-26 Genetic Laboratories, Inc. Preparation of animal tissues for surgical implantation in human recipients
US4637931A (en) * 1984-10-09 1987-01-20 The United States Of America As Represented By The Secretary Of The Army Polyactic-polyglycolic acid copolymer combined with decalcified freeze-dried bone for use as a bone repair material

Family Cites Families (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
DE2004553B1 (en) * 1970-02-02 1971-05-19 Fa B Braun, 3508 Melsungen Process for the production of guide rails from human or animal tissues for the restoration of damaged or destroyed specific tissue parts in the human and animal body

Patent Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0012959A1 (en) * 1978-12-16 1980-07-09 Intermedicat GmbH Method of preparation of collagen-based bone substitute material with improved biological stability and bone substitute material obtained by this method
DE3014123A1 (en) * 1980-04-12 1981-10-29 B. Braun Melsungen Ag, 3508 Melsungen Scleroprotein e.g. collagen, keratin or elastin transplants prodn. - involving treatment with glycerol or polyethylene glycol to improve biological stability
US4456589A (en) * 1982-07-08 1984-06-26 Genetic Laboratories, Inc. Preparation of animal tissues for surgical implantation in human recipients
US4637931A (en) * 1984-10-09 1987-01-20 The United States Of America As Represented By The Secretary Of The Army Polyactic-polyglycolic acid copolymer combined with decalcified freeze-dried bone for use as a bone repair material

Cited By (31)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0544926A1 (en) * 1990-06-20 1993-06-09 Chiron Adatomed Pharmazeutische und Medizintechnische Gesellschaft mbH Process and device for sterilizing implants
WO1997027882A1 (en) * 1996-01-31 1997-08-07 Steris Corporation Method of sterilization of bone tissue
US5788941A (en) * 1996-01-31 1998-08-04 Steris Corporation Method of sterilization of bone tussue
US5741782A (en) * 1996-03-29 1998-04-21 Cryolife, Inc. Antibiotic cocktail and method of use
FR2752382A1 (en) * 1996-08-16 1998-02-20 Assist Publ Hopitaux De Paris PROCESS FOR PROCESSING PRODUCTS OF HUMAN OR ANIMAL ORIGIN FOR THERAPEUTIC USE
WO1998007457A1 (en) * 1996-08-16 1998-02-26 Assistance Publique - Hopitaux De Paris Method for treating products of human or animal origin for therapeutic use
US9332750B2 (en) 1998-11-13 2016-05-10 Rti Surgical, Inc. Cyclic implant perfusion, cleaning and passivation process and implant produced thereby
US6482584B1 (en) 1998-11-13 2002-11-19 Regeneration Technologies, Inc. Cyclic implant perfusion cleaning and passivation process
US6613278B1 (en) 1998-11-13 2003-09-02 Regeneration Technologies, Inc. Tissue pooling process
US6652818B1 (en) 1998-11-13 2003-11-25 Regeneration Technologies, Inc. Implant sterilization apparatus
DE10026442A1 (en) * 2000-05-29 2001-12-13 Augustinus Bader Method of making a recipient-specific tissue graft
WO2001091819A1 (en) * 2000-05-29 2001-12-06 Augustinus Bader Method for producing a recipient-specific tissue transplant
KR20020011164A (en) * 2000-08-01 2002-02-08 이건일 Method for Manufacturing bone graft
US7645458B2 (en) 2001-01-04 2010-01-12 Osteotech, Inc. Method for sterilizing and/or deactivating adventitious agents associated with biological materials
WO2002070024A1 (en) * 2001-01-04 2002-09-12 Osteotech, Inc. Method for sterilizing bioactive materials
US7648676B2 (en) 2004-04-20 2010-01-19 Rti Biologics, Inc. Process and apparatus for treating implants comprising soft tissue
US8747736B2 (en) * 2006-07-13 2014-06-10 Abbott Cardiovascular Systems Inc. Reduced temperature sterilization of stents
US20110265426A1 (en) * 2006-07-13 2011-11-03 Advanced Cardiovascular Systems, Inc. Reduced Temperature Sterilization of Stents
US8309022B2 (en) * 2006-07-13 2012-11-13 Advanced Cardiovascular Systems, Inc. Reduced temperature sterilization of stents
US8475713B2 (en) 2006-07-13 2013-07-02 Advanced Cardiovascular Systems, Inc. Reduced temperature sterilization of stents
US8569726B2 (en) 2006-07-13 2013-10-29 Abbott Cardiovascular Systems Inc. Reduced temperature sterilization of stents
US20130309130A1 (en) * 2006-07-13 2013-11-21 Abbott Cardiovascular Systems Inc. Reduced temperature sterilization of stents
WO2008008436A1 (en) * 2006-07-13 2008-01-17 Abbott Cardiovascular Systems Inc. Reduced temperature sterilization of stents
EP2441475A1 (en) * 2006-07-13 2012-04-18 Abbott Cardiovascular Systems Inc. Reduced temperature sterilization of stents
US9339568B2 (en) 2006-07-13 2016-05-17 Abbott Cardiovascular Systems, Inc. Reduced temperature sterilization of stents
US10420652B2 (en) 2014-10-09 2019-09-24 Dr. Panagiotis Pedoulias Bone scaffold improvements
BE1024277B1 (en) * 2016-12-26 2018-01-11 Theracell Consulting Sprl Automated method for producing human or animal tissue for grafts.
WO2018122039A1 (en) * 2016-12-26 2018-07-05 Theracell Consulting Sprl Automated method for producing human or animal tissue for transplants
EP4079342A1 (en) * 2016-12-26 2022-10-26 Theracell Consulting SPRL Automated method for producing human or animal tissue for transplants
RU2785112C2 (en) * 2016-12-26 2022-12-02 Тераселл Консалтинг Спрл Automated method for obtaining human or animal tissues for transplantations
CN109191409A (en) * 2018-07-25 2019-01-11 北京市商汤科技开发有限公司 Image procossing, network training method, device, electronic equipment and storage medium

Also Published As

Publication number Publication date
JPH03170156A (en) 1991-07-23
EP0424159A3 (en) 1991-11-06

Similar Documents

Publication Publication Date Title
Singh et al. Radiation sterilization of tissue allografts: A review
US5788941A (en) Method of sterilization of bone tussue
US6652818B1 (en) Implant sterilization apparatus
US6613278B1 (en) Tissue pooling process
EP0424159A2 (en) Aseptic processing of allograft bone and tissue
EP0740555B1 (en) Preparation of bone for transplantation
EP1511445B1 (en) Sterilized xenograft tissue
WO2006074373A2 (en) Immunochemically modified and sterilized xenografts and allografts
RU2526429C1 (en) Method of manufacturing bone implants
WO2006041940A2 (en) Compositions having improved osteogenesis and methods for making and using same
Galea et al. Clinical effectiveness of processed and unprocessed bone
Hernigou et al. Influence of irradiation on the risk of transmission of HIV in bone grafts obtained from appropriately screened donors and followed by radiation sterilization
Angermann et al. Procurement, banking and decontamination of bone and collagenous tissue allografts: guidelines for infection control
Kaku et al. Influence of aeration, storage, and rinsing conditions on residual ethylene oxide in freeze-dried bone allograft
US20080038364A1 (en) Methods of processing body parts for surgery
Rozanov et al. Changes in the Morphological and Mechanical Characteristics of Bone Implants upon Radiation Sterilization
RU2630464C1 (en) Combined method for bone implants sterilisation
Singh et al. Gamma irradiated bone allografts processed from femoral heads
Malinin Allografts for the reconstruction of the cruciate ligaments of the knee: Procurement, sterilization, and storage
Delloye et al. Harvest, storage and microbiological security of bone allografts
Prolo et al. Efficacy and safety of ethylene oxide sterilization of allogeneic bone for human transplantation: a forty-year experience
Osborne et al. Skeletal Tissue: Specific Recovery and Processing Issues
Bank Types of Terminal Sterilization of Tissue Grafts
Hietala et al. Bone Transplantation Research Group, Medical School, University of Tampere and Department of Surgery, University of Oulu, Pinland" e-mail: tp56933Gutafi
Fujeríková et al. H. Mrázová, J. Koller, K. Kubišová

Legal Events

Date Code Title Description
PUAI Public reference made under article 153(3) epc to a published international application that has entered the european phase

Free format text: ORIGINAL CODE: 0009012

AK Designated contracting states

Kind code of ref document: A2

Designated state(s): BE DE FR GB IT NL

PUAL Search report despatched

Free format text: ORIGINAL CODE: 0009013

AK Designated contracting states

Kind code of ref document: A3

Designated state(s): BE DE FR GB IT NL

17P Request for examination filed

Effective date: 19920427

17Q First examination report despatched

Effective date: 19930318

STAA Information on the status of an ep patent application or granted ep patent

Free format text: STATUS: THE APPLICATION HAS BEEN REFUSED

18R Application refused

Effective date: 19930905